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Single-Cell Chromatin Accessibility Maps Reveal the Regulatory Programs Driving Early Mouse Organogenesis

ABSTRACT: Single-Cell Chromatin Accessibility Maps Reveal the Regulatory Programs Driving Early Mouse Organogenesis

PROVIDER: PRJNA550440 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10810776_1.fastq.gz	Fastqsanger.gz
	SRR10810776_2.fastq.gz	Fastqsanger.gz
	SRR9592390_1.fastq.gz	Fastqsanger.gz
	SRR9592390_2.fastq.gz	Fastqsanger.gz
	SRR9592391.fastq.gz	Fastqsanger.gz

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Single-Cell Chromatin Accessibility Maps Reveal the Regulatory Programs Driving Early Mouse Organogenesis

Project description:During early mouse embryonic development, pluripotent cells rapidly divide and diversify to construct the developing foetus, yet the underlying regulatory programs that define the cell repertoire for each organ remain ill-defined. To delineate comprehensive chromatin landscapes of mammalian lineages during early organogenesis, we mapped chromatin accessibility in 19,453 single nuclei from mouse embryos collected at 8.25 days post-fertilisation. Identification of cell type-specific regions of open chromatin pinpointed known regulatory regions and two new TAL1-bound endothelial enhancers, which we validated using transgenic mouse assays. Integrated gene expression and transcription factor motif enrichment analyses highlighted known and previously unrecognised cell type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a powerful role for the ETS transcription factor FEV in endothelial identity. Concerted in vivo validation experiments in mouse and zebrafish thus illustrate how single-cell open chromatin maps, representative of a mammalian embryo, provide access to the regulatory blueprint for mammalian organogenesis.

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Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.

Project description:During mouse embryonic development, pluripotent cells rapidly divide and diversify, yet the regulatory programs that define the cell repertoire for each organ remain ill-defined. To delineate comprehensive chromatin landscapes during early organogenesis, we mapped chromatin accessibility in 19,453 single nuclei from mouse embryos at 8.25 days post-fertilization. Identification of cell-type-specific regions of open chromatin pinpointed two TAL1-bound endothelial enhancers, which we validated using transgenic mouse assays. Integrated gene expression and transcription factor motif enrichment analyses highlighted cell-type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a role for the ETS factor FEV in endothelial identity downstream of ETV2 (Etsrp in zebrafish). Concerted in vivo validation experiments in mouse and zebrafish thus illustrate how single-cell open chromatin maps, representative of a mammalian embryo, provide access to the regulatory blueprint for mammalian organogenesis.

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Project description:Recent surveys of mouse organogenesis cell atlas (MOCA) with single cell transcriptomics have uncovered hundreds of cell types, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each cell type have yet to be elucidated. We applied a four-level combinatorial indexing assay, SPATAC-seq, to profile the chromatin accessibility in >350,000 cells derived from 13 embryos staged between embryonic day (E) 10.5 and 13.5 in a single experiment. The resulting map revealed the status of open chromatin for 844,817 candidate cis-regulatory elements (cCREs) in 33 main cell types and 296 subtypes. By integrating this accessible chromatin atlas with scRNA data of MOCA, we characterized the gene regulatory sequences and transcription factors associated with cell fate commitment, such as unreported role of Nr5a2 and Gata6 in gastrointestinal tract. Finaly, we integrated this atlas with previous scATAC-seq data from mouse embryos at E8.25 and 13 adult mouse tissues to dissect life stage specific gene regulatory programs across different cell types. This rich resource and comprerhensive analysis provide a foundation for expolring gene regulators in mammalian cell differentiation.

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